The objective of this grant is to further define the normal mammary epithelial (ME) antigens, to study their altered expression in breast neoplasia and the reason for it, and finally to identify the effect on ME cellular functions that such alterations cause. Mammary epithelial (ME) antigens have been discovered by us both in human (HME antigens) and in mouse (MME antigens). They are cell membrane components with cell-type specificity for normal mammary epithelial cells, that are also present in neoplastic ME cells. We will be using both models, human and mouse (that complement each other), to do the following: a) Continue to isolate and purify the ME antigens. This will be done using monoclonal antibodies of predefined specificity produced in hybrids between myeloma cells and spleen lymphocytes, the latter obtained from an animal immunized with mammary cell membrane components. Also, attempts will be made to separate ME antigens with the use of lectin affinity separation. b) Quantitate ME antigens with the aid of monoclonal antibodies in different stages and types of neoplasias trying to correlate levels and possible changes with the neoplastic phenotype. The quantitation will be done by indirect immunofluorescence, radioimmunoassay, cytotoxicity and flow cytofluorometry. c) Study how ME antigen expression (presence, diminution, absence) affects function in ME cells, in such areas as cell replication, differentiation and expression of the neoplastic phenotype. Further, we will continue our maintained effort at cell identification in the breast by extending our study of specific myoepithelial antigen(s) and fibrocyte antigen(s) of the breast, that we have just defined.